青少年成人脊髓性肌萎缩症临床诊疗指南
doi: 10.12376/j.issn.2097-0501.2023.01.010
崔丽英1,2,E-mail:pumchcuily@sina.com
Clinical Practice Guideline for Adolescent & Adult Patients with Spinal Muscular Atrophy
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摘要: 近年来,脊髓性肌萎缩症(SMA)在多学科综合管理、疾病修正治疗药物等方面取得长足进步,明显提升了患者生存期及生活质量。然而,对于年龄较大的青少年与成人患者尚缺乏系统性临床诊疗指南规范指导临床工作。基于循证医学原则,来自全国多家SMA诊疗中心的多学科专家经过充分讨论,达成一致意见,为SMA临床规范化诊疗提供重要依据。Abstract: In recent years, spinal muscular atrophy (SMA) has made progress in multidisciplinary treatment and disease-modifying therapeutic drugs, so that the progress has significantly improved the survival and quality of life of the patients. However, no clinical practice guideline has developed for the management of SMA in adults and adolescents patients. Experts of multidisciplinary from a number of tertiary medical centers in China who specialize in the diagnosis and treatment of SMA have come to an agreement based on evidence-based medicine. This guideline serves as instrumental reference for the standardized care of the Chinese SMA patients.
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表 1 推荐强度与证据级别标准
Table 1. Recommended intensity and level of evidence criteria
项目 分级 具体标准 推荐强度(分四级,Ⅰ级最强,Ⅳ级最弱) Ⅰ级 基于A级证据或专家高度一致的共识 Ⅱ级 基于B级证据和专家共识 Ⅲ级 基于C级证据和专家共识 Ⅳ级 基于D级证据和专家共识 治疗措施的证据等级(分四级,A级最高,D级最低) A级 基于多个随机对照试验的荟萃分析或系统评价;多个随机对照试验或1个样本量足够的机对照试验(高质量) B级 基于至少1个较高质量的随机对照试验 C级 基于未随机分组但设计良好的对照试验,或设计良好的队列研究或病例对照研究 D级 基于无同期对照的系列病例分析或专家意见 诊断措施的证据等级(分四级,A级最高,D级最低) A级 基于多个或1个样本量足够、采用了参考(金)标准、盲法评价的前瞻性队列研究(高质量) B级 基于至少1个前瞻性队列研究或设计良好的回顾性病例对照研究,采用了金标准和盲法评价(较高质量) C级 基于回顾性、非盲法评价的对照研究 D级 基于无同期对照的系列病例分析或专家意见 表 2 脊髓性肌萎缩症(SMA)国际分型
Table 2. International classification of spinal muscular atrophy(SMA)
分型 OMIM 起病年龄 运动里程碑 临床表现 亚型 自然病程 SMN2拷贝数 0型 - 出生前 无 仅有眼外肌活动,无任何活动。先天性关节挛缩,可合并先天性心脏病。出生后即需呼吸支持。 - 数日至1个月死亡 1 1型 253300 <6月龄 不能独坐 软婴,肢体无力、活动少。头面部肌肉力弱。钟型胸。反复出现呼吸道感染及呼吸衰竭。 1a:2周内发病,无头控能力1b:1~3月发病,无正常头控能力1c:3~6月发病,可获得头控能力 1a:半岁内死亡1b:2岁内死亡1c:中位生存期17岁 1a主要为11b主要为21c主要为3 2型 253550 6~18月龄 独坐,不能独站独走 运动发育明显落后。上肢肌力随年龄增长而下降,后期出现关节挛缩、脊柱侧凸、胸廓变形。 2a: 独坐能力短期获得,后期丧失2b: 独坐能力长期保持 超过70%存活至25岁以上 主要3 3型 253400 >18月龄 可独站独走 儿童期逐渐出现下肢近端起始,向上下发展的肢体无力萎缩,丧失行走能力后渐出现脊柱侧凸、关节挛缩、呼吸功能不全。 3a: 18~36月发病3b: >36月发病,进展更慢 存活至成年期,寿命轻度下降 3或4 4型 271150 成人期 获得跑跳等运动能力 成人起病,下肢起始的四肢近端力弱,病情缓慢进展。 - 寿命一般不受影响 ≥4 表 3 SMA国际分型(修订版)
Table 3. International classification of SMA (revised version)
分型 OMIM 起病年龄 运动里程碑 临床表现 亚型 自然病程 SMN2拷贝数 0型 - 出生前 无 仅有眼外肌活动,无任何活动。先天性关节挛缩,可合并先天性心脏病。出生后即需呼吸支持。 - 数日至1个月死亡 1 1型 253300 <6月龄 不能独坐 软婴,肢体无力、活动少。头面部肌肉力弱。钟型胸。反复出现呼吸道感染及呼吸衰竭。 1a:2周内发病,无头控能力1b:1~3月发病,无正常头控能力1c:3~6月发病,可获得头控能力 1a:半岁内死亡1b:2岁内死亡1c:中位生存期17岁 1a主要为11b主要为21c主要为3 2型 253550 6~18月龄 独坐,不能独站独走 运动发育明显落后。上肢肌力随年龄增长而下降,后期出现关节挛缩、脊柱侧凸、胸廓变形。 2a:独坐能力短期获得,后期丧失2b:独坐能力长期保持 超过70%存活至25岁以上 主要为3 3型 253400 >18月龄 可独站独走 儿童期逐渐出现下肢近端起始,向上下发展的肢体无力萎缩,丧失行走能力后渐出现脊柱侧凸、关节挛缩、呼吸功能不全。 3a:18~36月发病,10岁前丧失行走能力3b:>3岁发病,青春期前后病情明显加重,丧失行走能力。3c:>12岁发病,行走能力长期保持,终生无明显脊柱侧弯。 存活至成年期,生存期可能轻度缩短 3或4 4型 271150 >21岁 跑跳等所有运动能力 临床症状轻,运动及生活自理能力较正常人群无明显差异。 - 生存期一般不受影响 4或5 表 4 青少年成人SMA患者首次住院推荐评估项目
Table 4. Recommended assessment items for first hospitalization in adolescent adult SMA patients
类型 具体项目 生命体征与一般指标 体重
体温
心率
收缩压和舒张压
呼吸频率血液检验 1.血常规、尿常规+沉渣、便常规+潜血、8 h尿微量白蛋白
2.肝肾脂全、胱抑素C、肌酸激酶+肌酸激酶同工酶+肌红蛋白
3.凝血、感染4项4.血气分析
5.血β-人绒毛膜促性腺激素检查 1.X线或CT骨密度
2.脊柱CT+三维重建
3.全脊柱拼接相(拟行脊柱侧凸手术患者加做)
4.肺功能(通气+容量+弥散)
5.腰椎MRI
6.颈椎MRI(部分可能选择颈椎入路患者加做)
7.头MRI(除外其他可能合并疾病,监测药物治疗可能副作用)
8.超声心动图
9.心电图
10.肝胆胰脾双肾B超
11.胸部CT
12.电生理评估:复合肌肉动作电位(CMAP)、运动单位数量指数(MUNIX) 等量表及功能评估 详见康复评估部分(本刊后续报道) 脑脊液检测 蛛网膜下腔穿刺成功,确认脑脊液持续顺畅流出,测定脑脊液压力及滴速,留取脑脊液样本完善脑脊液常规、生化、细胞学、寡克隆区带检测,剩余样本分装后-80 ℃冰箱保存 -
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